Children with chromosome 22q11 deletion syndrome (22q11DS), a common neurodevelopmental disorder, have a remarkably high risk (25-40%) of developing schizophrenia and other psychotic disorders in late adolescence/adulthood. The psychotic disorders are preceded by neurocognitive deficits in childhood that are similar to that seen in individuals with schizophrenia. Based on recent research in neuroplasticity, we hypothesize that these deficits may be remediable by therapeutic cognitive interventions. We will conduct a pilot study, the aims of which are to adapt a neurocognitive and social cognitive training program specifically for children with 22q11DS, to assess feasibility and to gather preliminary data for a subsequent randomized controlled trial to evaluate the efficacy of cognitive remediation in mitigating the cognitive and social deficits in these individuals. Our approach is two-pronged, consisting of a computer-based training program designed to improve neurocognition through visual and auditory tasks, and a small-group intervention designed to improve social cognition. These approaches have been effective in adults with cognitive deficits and with schizophrenia and we now seek to adapt them to children with 22q11DS, who have exceptional needs due to their young age and high risk of psychosis. An open-labeled, randomized study will be performed, involving 18 children with 22q11DS and 18 control subjects, ages 12-17 years. The participants will undergo sequential computerized neurocognitive and social cognitive training for the duration of one year, with assessments of these domains before and after the interventions. Data collected from this pilot project will be used for a larger scale evaluation of the efficacy of cognitive remediation in individuals with 22q11DS. The proposed research is highly innovative, since there are no current treatments for the cognitive deficits in 22q11DS;additionally the combined neurocognitive and social cognitive approach in children with 22q11DS is novel. We believe that the development of a cognitive remediation program explicitly for children with 22q11DS is significant, since it would have the potential to mitigate the cognitive deficits that are an integral part of the childhood problems and may in the future be effective in modifying the cognitive decline associated with the onset of psychosis. PUBLIC HEALTH RELEVANCE: The purpose of this project is to adapt a cognitive remediation program that is uniquely suited for children with 22q11.2 deletion syndrome, to test its feasibility and to gather preliminary data for a future study designed to examine efficacy of such cognitive intervention.